PROJECT SUMMARY/ABSTRACT The broad goal of the Pre-clinical/Co-clinical Core is to advance development of mouse models of specific diseases in The Jackson Laboratory (JAX) Precision Genetics Center (JPGC) by promoting the interactions with clinicians and hospitals, access to patient data and samples and comprehensive model assessment necessary for generation of models ready for preclinical testing. JAX investigators have expertise in mammalian biology, genetics and the disease areas in which they work. This is reflected in the expertise of the JPGC Project Leaders, who together with their research teams will develop new models in six disease areas, in six research projects. Because JAX is not a medical center, JAX investigators and JAX as an institution have established collaborations with investigators at hospitals and clinical laboratories worldwide, have established resources for access to human patient samples and have developed and implemented pipelines for evaluation of preclinical mouse models. The Pre-clinical/Co-clinical Core will support the preclinical and clinical interactions necessary for model generation in the JPGC by enhancing existing interactions and model- generation procedures, and by bringing in new clinical partners and incorporating new preclinical testing paradigms. Specifically, the Core will: Aim 1) Facilitate access to clinical data and samples, as appropriate for research project objectives. Incorporate the ability to implant human material into mice when appropriate for new precision disease models; Aim 2) Promote research-clinical partnerships and team-building: Facilitate interactions between research scientists and clinical collaborators to identify project-specific and program-wide solutions; and Aim 3) Track project progress to identify the most promising pipelines that most tangibly inform future clinical applications. This Core will accomplish these aims by enhancing interactions with the two existing sites at JAX that are CLIA-registered as clinical laboratories qualified to accept and process clinical samples and data; building new and expanded partnerships with clinicians; and optimizing preclinical model development by selecting particularly promising models generated in JPGC projects for assessment and refinement in a preclinical testing pipeline that we will develop based on established procedures in the In Vivo Pharmacology Service and other high-throughput units at JAX. Together, these Core functions will ensure that developed disease models and platforms are appropriate and ready for preclinical testing.